ArticleCell death & disease2022
The alternative splicing of intersectin 1 regulated by PTBP1 promotes human glioma progression.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- ARGLU1 in Glioma: A Novel Potential Regulator of Splicing, DNA Repair, and Therapeutic Resistance.Cells · 2026Review
- PTBP1 and Cancer: From RNA Regulation to Therapeutic Potential.Journal of cellular and molecular medicine · 2025Review
- The emerging roles of aberrant alternative splicing in glioma.Cell death discovery · 2025Review
- PTBP1 as a potential regulator of disease.Molecular and cellular biochemistry · 2024Review
- Downregulation of Splicing FactorCurrent issues in molecular biology · 2024Article
- Alternative splicing analysis of lignocellulose-degrading enzyme genes and enzyme variants in Aspergillus niger.Applied microbiology and biotechnology · 2024Article
- Research Progress on the Structural and Functional Roles of hnRNPs in Muscle Development.Biomolecules · 2023Review
- The KMT2A recombinome of acute leukemias in 2023.Leukemia · 2023Article
- LncRNA AC006064.4-201 serves as a novel molecular marker in alleviating cartilage senescence and protecting against osteoarthritis by destabilizing CDKN1B mRNA via interacting with PTBP1.Biomarker research · 2023Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intersectin 1 (ITSN1) contains two isoforms: ITSN1-S and ITSN1-L, which are highly regulated by alternative splicing. Our previous results showed that the two isoforms of ITSN1 displayed opposite functions: ITSN1-S promoted glioma development, while ITSN1-L exerted an inhibitory role in glioma progression. In this study, our transcriptome analysis using a large glioma cohort indicated that the ratio of ITSN1-S/ITSN1-L was positively correlated with glioma grading and poor prognosis. We identified the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) as an ITSN1 pre-mRNA interaction protein through RNA pull-down assay and RNA immunoprecipitation assay. Knockdown of PTBP1 decreased the ratio of ITSN1-S/ITSN1-L. Minigene reporter assay and mutation analyses further confirmed PTBP1 targeted polypyrimidine sequences on ITSN1 exon 30 (TTGCACTTCAGTATTTT) and promoted the inclusion of ITSN1 exon 30. Subsequently, silencing PTBP1 inhibited glioma cell proliferation, migration, and invasion by down-regulating the ratio of ITSN1-S/ITSN1-L. Taken together, our study provides a novel mechanism that PTBP1 modulates the alternative splicing of ITSN1 and promotes glioma proliferation and motility by up-regulating the ratio of ITSN1-S/ITSN1-L, thereby highlighting that PTBP1 may be an attractive therapeutic target for gliomas.
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